Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Venous Thromboembolism in Patients with Type 2 Diabetes: A Cohort Study

Am J Med. 2021 May;134(5):606-613.e6. doi: 10.1016/j.amjmed.2020.10.046. Epub 2020 Dec 11.

Abstract

Purpose: We assessed whether sodium-glucose co-transporter type 2 (SGLT2) inhibitors are associated with a higher incidence rate of venous thromboembolism in patients with type 2 diabetes.

Methods: We conducted a population-based cohort study using the InGef database including patients with type 2 diabetes newly treated with noninsulin antidiabetic drugs between 2012 and 2018. Cases of venous thromboembolism identified during follow-up were matched to 40 controls on age, sex, cohort entry date, and duration of follow-up. Using a nested case-control approach, conditional logistic regression estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) of venous thromboembolism adjusted for sociodemographic and clinical variables, comparing current use of SGLT2 inhibitors with current use of dipeptidyl peptidase-4 (DPP-4) inhibitors.

Results: In a cohort of 219,538 patients, we identified 2152 cases of venous thromboembolism and matched them to 85,104 controls. Compared with DPP-4 inhibitors, current use of SGLT2 inhibitors was associated with a lower rate of venous thromboembolism (RR, 0.75; 95% CI, 0.59-0.94). Effect estimates were similar for dapagliflozin (RR, 0.77; 95% CI, 0.57-1.03) and empagliflozin (RR, 0.71; 95% CI, 0.52-0.98).

Conclusions: Compared with DPP-4 inhibitors, SGLT2 inhibitors were not associated with a higher rate of venous thromboembolism, providing reassurance regarding their thromboembolic safety.

Keywords: Antidiabetic drugs; Pharmacoepidemiology; Real-world evidence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Logistic Models
  • Male
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Venous Thromboembolism / chemically induced*

Substances

  • Sodium-Glucose Transporter 2 Inhibitors